Azoospermia: etiology, pathogenesis, prevalence of forms and algorithm for differential diagnostics

Introduction. Azoospermia, defined as the absence of spermatozoa in the ejaculate after centrifugation, is one of the leading causes of male infertility, affecting approximately 1,0 % of men in the general population and up to 15,0 % of infertile patients. Timely differentiation between obstructive (ОА) and non-obstructive (NOA) azoospermia is critical for selecting appropriate treatment strategies, determining prognosis, and applying assisted reproductive technologies (ART).

Aim: to investigate the prevalence of different azoospermia forms of azoospermia in infertile men, within the context of real-world clinical practice at a non-specialized endocrine outpatient department, including personal observations, with consideration of/in comparison with the results of international and Russian epidemiological studies.

Materials and Methods. A comprehensive analysis of literature, clinical guidelines, and original data was performed. The study included 450 men aged 25–45 years with confirmed azoospermia. All patients underwent a comprehensive examination, including collection of anamnesis (reproductive, somatic, surgical); physical examination with assessment of secondary sexual characteristics, size and consistency of the testicles; double examination of ejaculate (centrifugation, microscopy); examination of blood hormone levels (follicle-stimulating hormone, luteinizing hormone, total testosterone, prolactin, anti-Müllerian hormone, sex hormone-binding globulin, inhibin B; if indicated – estradiol, thyroid-stimulating hormone, thyroxine); scrotum ultrasound examination with Doppler ultrasonography; genetic testing – karyotyping, testing for microdeletions of Y chromosome azoospermia factor (AZF) of the Y chromosome, CFTR (cystic fibrosis transmembrane conductance regulator) gene testing; when indicated, testicular sperm extraction (TESE) biopsy was performed.

Results. NOA and OA were identified in 63.3 % and 30 % of patients, respectively. Among NOA cases, the leading causes were idiopathic forms (19.6 %), Klinefelter syndrome (8.4 %), Y-chromosome microdeletions (5.8 %), and hypogonadotropic hypogonadism (6.7 %). Varicocele was associated with NOA in 12 % of cases. These findings are consistent with global data, although minor ethnic and methodological differences were observed.

Conclusion. Azoospermia is a clinically and etiologically heterogeneous condition. Timely differentiation between its forms and the inclusion of genetic testing improve diagnostic accuracy and help optimizing management strategies. Standardization of diagnostic algorithms and a personalized approach increase ART effectiveness and the likelihood of fertility restoration.

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